Egyptian Pediatric Guidelines for the Management of Children with Isolated Thrombocytopenia Using the Adapted ADAPTE Methodology-A Limited-Resource Country Perspective.

BACKGROUND: Thrombocytopenia is a prevalent presentation in childhood with a broad spectrum of etiologies, associated findings, and clinical outcomes. Establishing the cause of thrombocytopenia and its proper management have obvious clinical repercussions but may be challenging. This article provides an adaptation of the high-quality Clinical Practice Guidelines (CPGs) of pediatric thrombocytopenia management to suit Egypt's health care context. METHODS: The Adapted ADAPTE methodology was used to identify the high-quality CPGs published between 2010 and 2020. An expert panel screened, assessed and reviewed the CPGs and formulated the adapted consensus recommendations based on the best available evidence. DISCUSSION: The final CPG document provides consensus recommendations and implementation tools on the management of isolated thrombocytopenia in children and adolescents in Egypt. There is a scarcity of evidence to support recommendations for various management protocols. In general, complete clinical assessment, full blood count, and expert analysis of the peripheral blood smear are indicated at initial diagnosis to confirm a bleeding disorder, exclude secondary causes of thrombocytopenia and choose the type of work up required. The International Society of Hemostasis and thrombosis-Bleeding assessment tool (ISTH-SCC BAT) could be used for initial screening of bleeding manifestations. The diagnosis of immune thrombocytopenic purpura (ITP) is based principally on the exclusion of other causes of isolated thrombocytopenia. Future research should report the outcome of this adapted guideline and include cost-analysis evaluations.

Transfusion of blood components in pediatric age groups: an evidence-based clinical practice guideline adapted for the use in Egypt using 'Adapted ADAPTE'.

Pediatric transfusion is a complex area of medicine covering a wide age range, from neonates to young adults. Compared to adult practice, there is a relative lack of high-quality research to inform evidence-based guidelines. We aimed to adapt the pre-existing high-quality practice guidelines for the transfusion of blood components in different pediatric age groups to be available for national use by general practitioners, pediatricians, and other health care professionals. The guideline panel included 17 key leaders from different Egyptian institutions. The panel used the Adapted ADAPTE methodology. The panel prioritized the health questions and recommendations according to their importance for clinicians and patients. The procedure included searching for existing guidelines, quality appraisal, and adaptation of the recommendations to the target context of use. The guideline covered all important aspects of the indications, dosing, and administration of packed red cells, platelets, and fresh frozen plasma. It also included transfusion in special situations, e.g., chronic hemolytic anemia and aplastic anemia, management of massive blood loss, malignancies, surgery, recommendations for safe transfusion practices, and recommendations for modifications of cellular blood components. The final version of the adapted clinical practice guideline (CPG) has been made after a thorough review by an external review panel and was guided by their official recommendations and modifications. A set of implementation tools included algorithms, tables, and flow charts to aid decision-making in practice. This adapted guideline serves as a tool for safe transfusion practices in different pediatric age groups.

Glycemic variability and time in range among children with type 1 diabetes on insulin pump during the Covid-19 pandemic in Egypt; single center experience.

BACKGROUND: Covid-19 has impacted the lives of individuals worldwide especially those with chronic illnesses. Children with type 1 diabetes (T1DM) are at risk of glycemic deterioration during the Covid-19 pandemic. However, some studies reported glycemic improvement in these children during the pandemic. AIM: To assess the impact of Covid-19 on glycemic control and acute complications among children with T1DM on insulin pump in Egypt. METHODOLOGY: Forty-two children with T1DM on insulin pump for at least 1 year were assessed during the period from June 2020 to May 2021 for insulin requirements, insulin-pump problems, frequency of diabetic-ketoacidosis (DKA), hypoglycemia and HbA1C. Continuous-glucose monitoring was done using Medtronic i-pro device for 5 days. Data were compared to those obtained from the patients' medical records 1 year previously. RESULT: Upon comparing data during Covid-19 pandemic with previous data from 12-24 months before Covid-19, there was a significant small increase in the mean total daily insulin dose from 0.83 ± 0.28 to 0.88 ± 0.30 U/kg/day with a similar small increase in the mean basal percentage from 51.19 ± 3.46 to 52.74 ± 4.31. Interestingly, the median time in range showed small increase from 53 (IQR 47-61) to 57.0 (IQR 51-73), the mean coefficient of variation showed small decrease from 42.10 ± 9.90 to 38.20 ± 8.12 and the mean HbA1C significantly decreased from 8.8 ± 1.3 (72.31 ± 16.78 mmol/ml) to 7.8 ± 1.2 mg/dl (61.31 ± 16.62 mmol/mol). Twenty-nine children (69%) had insulin-pump problems in the form of skin irritation (31%), skin infection (7.1%) and pump Set/Site occlusion (31%). CONCLUSION: No safety issues and overall glycemic improvement were reported among the children with T1DM on insulin pump therapy from this single center during the covid-19 pandemic.

Assessment of fibroblast growth factor 21 in children with type 1 diabetes mellitus in relation to microvascular complications.

INTRODUCTION: Type 1 diabetes mellitus (DM1) represents a growing global health problem with significant morbidity. Fibroblast growth factor 21 (FGF21) is an adipokine expressed predominantly in the liver that plays an important role in metabolic regulation. AIM OF THE STUDY: This study assesses FGF21 levels in children with DM1, in comparison to controls, and correlates them with diabetes duration, glycated haemoglobin (HbA1c), and diabetic microvascular complications. MATERIAL AND METHODS: Fifty children with DM1, aged between 5 and 16 years, were studied regarding their diabetes duration, HbA1c, urinary albumin creatinine ratio (UACR), fundus, and FGF21 level. They were compared to 50 healthy controls. RESULTS: The median FGF21 of the studied children with DM1 was 150 pg/ml, range 50-350 pg/ml; while that of the controls was 35 pg/ml, range 20-50 pg/ml. FGF21 level was significantly higher in children with DM1 than in controls ( p < 0.001). Moreover, it was significantly and positively correlated with diabetes duration, mean blood glucose level, and HbA1c ( p < 0.001, p = 0.015, p = 0.018, respectively). Interestingly, the FGF21 level was not significantly elevated in children with DM1 having diabetic nephropathy and retinopathy ( p = 0.122, p = 0.298, respectively). CONCLUSIONS: FGF21 is significantly higher among children with DM1 than in controls. However, its role in diabetic microvascular complica-tions needs further assessment.

The efficacy of insulin degludec and insulin glargine over NPH insulin among toddlers and preschoolers with type 1 diabetes using glycemic variability and time in range.

Optimizing glycemic control without risking hypoglycemia is crucial in toddlers and preschoolers with type 1 diabetes (T1D) to avoid cognitive impairment later in life. Hence, this study aims to compare glycemic parameters among toddlers and preschoolers with T1D in relation to different basal insulins. Sixty toddlers and preschoolers with T1D with mean age of 3.53 ± 1.17 years (range, 2-6) and mean diabetes duration of 9.37 ± 1.85 months were randomly assigned into three equal groups; group A received insulin degludec, group B received insulin glargine, and group C were on NPH. At baseline, the three groups were matched regarding clinical and laboratory parameters (p > 0.05). They were followed up at 3 and 6 months for insulin daily dose (IDD), hypoglycemia and severe-hypoglycemia frequency, and glycated hemoglobin (HbA1c). At the study endpoint, continuous glucose monitoring (CGM) was assessed in a random sample of 10 patients from each group. The mean time in range (TIR) of the studied cohort was 55.07 ± 24.05%, and their mean coefficient of variation (CV) was 42.82 ± 11.69%. The TIR was significantly higher in the degludec group (69.36 ± 18.54) and the glargine group (55.43 ± 26.51) than the NPH group (32.56 ± 9.11), p < 0.001. Meanwhile, the CV was significantly lower in the degludec group (35.12 ± 6.47) than the gargine (44.1 ± 13.13) and the NPH (53.8 ± 7.54) groups, p < 0.001. The insulin degludec and glargine groups had significantly lower HbA1c (p = 0.002), hypoglycemia (p = 0.006), severe hypoglycemia (p = 0.029), and IDD (p = 0.015) than the NPH group. CONCLUSION: Insulin degludec and glargine resulted in better HbA1c and TIR with reduced hypoglycemia and IDD than NPH among toddlers and preschoolers with T1D. Moreover, CV was lowest in the insulin degludec group. WHAT IS KNOWN: • Insulin therapy is the mainstay of T1D management. • Optimal insulin therapy for young children with T1D should provide effective glycemic. WHAT IS NEW: • Insulin degludec and insulin glargine have better efficacy than NPH insulin among toddlers and preschoolers with T1D in the term of significantly lower coefficient of variation, HbA1c and IDD and significantly higher time in range. • Insulin degludec and insulin glargine have better safety in the term of less hypoglycemia and severe hypoglycemia episodes than NPH insulin among toddlers and preschoolers with T1D.

BCL11A Polymorphism in Egyptian Children with ß-Thalassemia: Relation to Phenotypic Heterogeneity.

Fetal hemoglobin (HbF) is a potent genetic modifier of ß-thalassemia phenotype. B-cell lymphoma 11A ( BCL11A ) gene results in significant silencing of HbF. The aim of this study was to assess the prevalence of different BCL11A genotypes among a cohort of Egyptian children with ß-thalassemia and to correlate them to HbF and clinical severity score. Eighty-two children with ß-thalassemia (aged 12.95 ± 3.63 years) were recruited from the Pediatric Hematology Clinic, Ain Shams University. They were divided based on the clinical severity of ß-thalassemia into three subgroups: 20 mild (24.4%), 24 moderate (29.3%), and 38 severe (46.3%). Age, gender, age of diagnosis, initial HbF level, transfusion history, and history of splenectomy were assessed. Anthropometric measures, signs of anemia and hemosiderosis, and the severity score were determined. Laboratory investigations such as complete blood picture, ferritin, and single gene polymorphism genotyping of the rs11886868 were also performed. Our findings showed that 16 children had CC genotype (19.5%), 38 had TC genotype (46.3%), and 28 had TT genotype (34.1%) of the rs#. ß-thalassemia children with TT genotype had significantly higher severity scoring than the other two groups ( p < 0.001). Moreover, mean initial HbF was found to be lower in children with TT genotype followed by TC and CC genotypes ( p < 0.001). Increased γ-globin expression associated with BCL11A gene polymorphism is associated with better clinical severity of ß-thalassemia.

Changes in early optical coherence tomography angiography among children and adolescents with type 1 diabetes: Relation to fibroblast growth factor 21.

AIMS: Current diagnostic and treatment modalities target late stages of diabetic retinopathy (DR) when retinopathy has already been established. Novel and more sensitive strategies are needed. Optical coherence tomography angiography (OCTA) permits non-invasive visualisation of retinal microcirculation. Fibroblast growth factor-21 (FGF21) plays an important role in glucose and lipid homoeostasis. This study assesses early OCTA changes among children and adolescents with type 1 diabetes (T1DM) compared to fundus photography and correlates them to diabetes-duration, glycaemic control, and FGF21; hence, it determines their value in early detection of DR. METHODOLOGY: Hundred children and adolescents with T1DM were assessed for diabetes-duration, insulin therapy, hypoglycemia, and diabetic-ketoacidosis frequency, Tanner staging, glycated-haemoglobin (HbA1c), fasting lipids, urinary albumin/creatinine ratio, and serum FGF21. OCTA and fundus photography were done for the studied patients and 100 age, gender, and Tanner matched healthy controls. RESULTS: The mean age of the children and adolescents with T1DM was 10.84 years, their mean diabetes-duration was 3.27 years and their median FGF21 was 150 pg/ml. FGF21 was significantly higher among children and adolescents with T1DM than controls (p < 0.001). Children and adolescents with T1DM had a significantly larger foveal avascular zone (FAZ) and lower peripapillary and inside-disc capillary densities (p < 0.05); with no significant fundus photography difference (p = 0.155) than controls. FAZ was positively correlated and peripapillary and inside-disc capillary densities were negatively correlated with diabetes-duration, HbA1c, FGF21, and Tanner stage. FGF21 was significantly higher in T1DM children and adolescents having OCTA changes compared to those with normal OCTA (p = 0.002). Multivariate-regression revealed that FAZ is independently associated with diabetes-duration, HbA1c and FGF21. CONCLUSIONS: OCTA changes start early in children and adolescents with T1DM long before the fundus changes. These changes are correlated with diabetes-duration, puberty, glycaemic, and FGF21.

Metabolism and memory: α-synuclein level in children with obesity and children with type 1 diabetes; relation to glucotoxicity, lipotoxicity and executive functions.

BACKGROUND/OBJECTIVES: Children with obesity and those with type 1diabetes (T1D) exhibit subtle neurocognitive deficits, the mechanism of which remains unknown. α-synuclein plays a fundamental role in neurodegeneration. Moreover, its role in glucose and lipids metabolism is emerging. This study aims to assess whether α-synuclein is correlated with the degree of neurodegeneration in children with obesity and those with T1D in comparison to healthy controls and correlate it to various neurocognitive and metabolic parameters. SUBJECTS/METHODS: Forty children with obesity, 40 children with T1D and 40 matched-healthy controls were assessed for anthropometric measurements and blood-pressure. Cognitive evaluation was performed using Stanford-Binet scale and Barkley Deficits in Executive Functioning (EF) Scale-Children and Adolescents. α-synuclein, fasting lipids and glucose were measured with calculation of the homeostatic model of insulin-resistance and estimated-glucose disposal rate. RESULTS: Children with obesity and those with T1D had significantly higher α-synuclein (p < 0.001) and total EF percentile (p = 0.001) than controls. α-synuclein was negatively correlated to total IQ (p < 0.001 and p = 0.001), and positively correlated with total EF percentile (p = 0.009 and p = 0.001) and EF symptom count percentile (p = 0.005 and p < 0.001) in children with T1D and obesity, respectively. Multivariate-regression revealed that α-synuclein was independently related to age (p = 0.028), diabetes-duration (p = 0.006), HbA1C% (p = 0.034), total IQ (p = 0.013) and EF symptom count percentile (p = 0.003) among children with T1D, and to diastolic blood-pressure percentile (p = 0.013), waist/hip ratio SDS (p = 0.007), total EF percentile (P = 0.033) and EF symptom count percentile (p < 0.001) in children with obesity. CONCLUSION: α-synuclein could have a mechanistic role in neurocognitive deficit among children with obesity and T1D.

Leukocytic dysregulation in children with type 1 diabetes: relation to diabetic vascular complications.

Background: Growing evidences highlight the role of the innate immune response in the pathogenesis of type 1 diabetes (T1D) vascular complications. Neutrophil lymphocytic ratio (NLR) and platelet lymphocytic ratio (PLR) are inexpensive but novel markers of chronic inflammation might have prognostic value in children with T1D. Aim: To study NLR and PLR levels in children with T1D in comparison to matched controls and correlate them with fraction-C of glycosylated hemoglobin (HbA1C) and micro-vascular complications. Methodology: Hundred children with T1D were compared to 100 matched healthy controls. History included diabetes duration, insulin dose and frequency of hypoglycemic attacks. Fundus examination and the simple rapid neuropathy disability score were done. HbA1C, fasting lipids, urinary albumin excretion and complete blood count were measured with assessment of NLR and PLR. Results: NLR was significantly higher (p = 0.008) and PLR was significantly lower (p = 0.007) in children with T1D than controls. NLR was positively correlated while PLR was negatively correlated with HbA1C, diabetes duration, fasting cholesterol, triglycerides and LDL. NLR was significantly higher (p < 0.001) and PLR was significantly lower (p = 0.005) in children with microvascular complications than those without. Moreover, multivariate logistic regression revealed that microvascular complications were independently associated with NLR (p = 0.013) and PLR (p = 0.004). Conclusion: Children with T1D had significantly higher NLR and lower PLR compared to controls. These changes were more evident in those with diabetic microvascular complications than those without. Furthermore, NLR was positively correlated and PLR was negatively correlated to HbA1C, diabetes duration and hyperlipidemia. Hence, NLR and PLR can be a potential indicator for the risk of development of diabetic microvascular complications in children with T1D.

Psychosocial aspects of continuous subcutaneous insulin infusion in children with type 1 diabetes in Egypt; a limited resources country perspective.

BACKGROUND: Novel innovations continue to emerge in type-1 diabetes (T1D) management aiming to improve glycemic control. Assessing the psychosocial outcomes of different treatment modalities is specifically crucial among children with T1D and differs from one population to another. OBJECTIVES: To compare the health related quality of life (HRQoL) and confidence in diabetes self-management (CIDS) among children with T1D on continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) and to correlate them with the efficacy of glycemic control, Mini-International Neuropsychiatric Interview for Children and Adolescents(MINI-KID) depression module and socioeconomic-standard scale. METHODS: This real life study (ClinicalTrials.gov number NCT04756011) included 60 children with T1D (30 on CSII and 30 on MDI), aged 6-18 years. Disease duration, insulin therapy, average self-monitoring of blood glucose (SMBG) and HbA1C were assessed. CIDS, socioeconomic-standard, MINI-KID depression and HRQoL scales were applied. RESULTS: Children with T1D on CSII have significantly higher HRQoL and CIDS than those on MDI (P < 0.001). A significant negative correlation is found between HRQoL and insulin daily dose(P = 0.022), HbA1C(P < 0.001), average SMBG(P < 0.001) and MINI-KID depression scale(P < 0.001). A significant positive correlation is found between HRQoL and CIDS(P < 0.001) and health care, home sanitation, family possessions and occupation socioeconomic scores(P = 0.033, P = 0.001, P < 0.001 and P = 0.006, respectively). Multivariate regression analysis revealed that HRQoL is most associated with MINI-KID depression scale (P = 0.004) and annual total cost(P < 0.001). CONCLUSION: Children with T1D on CSII have significantly better HRQoL, CIDS and HbA1C with less depression than those on MDI.

Nail fold microangiopathy in adolescents with type 1 diabetes: Relation to diabetic vascular complications.

OBJECTIVES: Microangiopathy is implicated in the pathogenesis of diabetic vascular complications. Nail fold videocapillaroscopy (NVC) is an easy non-invasive tool of microvasculature assessment. This study compares the NVC changes in adolescents with Type1 diabetes (T1D) to healthy controls and correlates them to diabetic vascular complications. METHODS: Hundred thirty-five adolescents with T1D (disease duration 5 years) were compared to 135 matched controls. Diabetes duration, insulin therapy, fundus, and Toronto clinical scoring system (TCSS) were assessed. Fasting lipids, fraction-C of glycosylated hemoglobin (HbA1C), urinary albumin creatinine ratio (UACR), nerve conduction velocity, and NVC were performed. RESULTS: NVC changes were found in 120 adolescents with T1D (88.8%). These changes were significantly higher in adolescents with T1D than controls (p < .001). Significant positive relation was found between NVC changes and TCSS (p = .006), diabetes duration (p = .001), HbA1C (0.008), cholesterol (p = .011), LDL (0.016), UACR (p < .001), and nerve conduction velocity (p < .001). Multivariate logistic regression study revealed that diabetic nephropathy and neuropathy were independently associated with NVC changes (p < .001 and p = .007, respectively). CONCLUSION: Adolescents with T1D have significantly higher NVC changes than controls. These changes were more evident in those having vascular complications than those without. Thus, NVC can be a potential non-invasive tool for early assessment and follow-up of the microvasculature among adolescents with T1D.

Inhibition of the Vancomycin Resistance in Staphylococcus aureus in Egypt Using Silver Nanoparticles.

Staphylococcus aureus is a major human pathogen that is sometimes resistant to vancomycin. In this study, the prevalence of vancomycin-resistant Staphylococcus aureus (VRSA) was studied. 100 isolates of S. aureus were identified based on biochemical and molecular evidence. The antibiotic susceptibility of the studied isolates was tested against 13 antibiotics by the disc diffusion method that showed 24 vancomycin-resistant isolates. The minimum inhibitory concentrations (MICs) were estimated by the agar dilution method to determine vancomycin intermediate-resistant S. aureus (VISA) and VRSA. The resistance gene cluster (vanA, vanR, vanH, and vanY) was amplified by PCR and then sequenced. Amplification of vanA and vanR genes showed that they are present in 21.4% and 14.3% of VRSA isolates, respectively, whereas none of the studied genes has been detected in VISA strains. A significant antimicrobial effect toward VRSA isolates using silver nanoparticles (AgNPs) synthesized from S. aureus and rosemary leaves was recorded. This study confirmed the existence of VRSA strains in Egypt. Furthermore, the use of silver nanoparticles inhibits these vancomycin-resistant S. aureus strains in vitro.

Pancreatic shear wave elastography in children with type 1 diabetes: relation to diabetes duration, glycemic indices, fasting C-peptide and diabetic complications.

BACKGROUND: Little is known about changes in the pancreas as the course of type 1 diabetes progresses. Recently, shear wave elastography (SWE) emerged as a tool for assessing pancreatic stiffness in chronic pancreatitis and pancreatic cancer with a few studies assessing it in diabetes. OBJECTIVE: To compare pancreatic SWE in children with recent-onset and long-standing type 1 diabetes to healthy controls and to correlate it with diabetes duration, glycated hemoglobin (HbA1C), functional B cell reserve (fasting C-peptide) and diabetic complications. MATERIALS AND METHODS: Fifty children with type 1 diabetes (25 with recent-onset and 25 with long-standing type 1 diabetes) and 50 controls were enrolled. Diabetes duration, insulin therapy, fundoscopic examination of the eyes and the neuropathy disability score were assessed. Fasting C-peptide, lipids, HbA1C and urinary albumin-creatinine ratio were measured. Pancreatic SWE was measured using the General Electric Logiq P9 ultrasound system. RESULTS: The mean SWE of the studied children with recent-onset type 1 diabetes was 4.81±0.62 kilopascals (Kpa), those with long-standing type 1 diabetes was 7.10±1.56Kpa and for controls was 5.57±0.27 Kpa (P<0.001). SWE was positively correlated to diabetes duration (P<0.001) and negatively correlated to fasting C-peptide (P<0.001). Regarding diabetes complications, SWE was positively correlated to frequency of severe hypoglycemia (P=0.005), HbA1C (P=0.03), low-density lipoproteins (P<0.001) and cholesterol (P<0.001) and significantly related to diabetic neuropathy (P=0.04) and nephropathy (P=0.05). Diabetes duration, fasting C-peptide, HbA1C and frequency of severe hypoglycemia were the significant independent variables related to SWE increase by multivariable regression analysis. CONCLUSION: Pancreatic SWE changes significantly with duration of type 1 diabetes, being lowest in those with recent-onset type 1 diabetes and highest in those with long-standing type 1 diabetes, particularly those with diabetic nephropathy and neuropathy.

Disordered eating behaviour in adolescents with type 1 diabetes on continuous subcutaneous insulin infusion; relation to body image, depression and glycemic control.

BACKGROUND: Disordered eating behaviour (DEB) represents a significant morbidity among people with type-1 diabetes (T1D). Continuous-subcutaneous insulin infusion (CSII) improves glycemic control and psychological wellbeing in those with T1D. However, its relation to DEB remains obscure. OBJECTIVES: To compare DEB among adolescents with T1D on CSII versus basal-bolus regimen and correlate it with body image, HbA1C and depression. METHODS: Sixty adolescents with T1D (30 on CSII and 30 on basal-bolus regimen), aged 12-17 years were studied focusing on diabetes-duration, insulin therapy, exercise, socioeconomic standard, hypoglycemic attacks/week and family history of psychiatric illness. Anthropometric measures, HbA1C, binge eating scale (BES), body image tool, patient health questionnaire-9 (PHQ9) and the Mini-KID depression scale were assessed. RESULTS: Among the studied adolescents with T1D, six had DEB (10%), 14 had poor body-image perception (23.3%), 42 had moderate body-image perception (70%) and 22 had depression (36.7%). Adolescents with T1D on CSII had significantly lower BES (p = 0.022), Mini-KID depression (p = 0.001) and PHQ9 (p = 0.02) than those on basal-bolus regimen. BES was positively correlated to depression (p < 0.001), HbA1C (p = 0.013) and diabetes-duration (p = 0.009) and negatively correlated to body-image (p = 0.003). CONCLUSION: DEB is a prevalent comorbidity among adolescents with T1D, with higher frequency in those on basal-bolus regimen than CSII.

Disordered eating behaviour is a significant morbidity among people with type 1 diabetes. It is associated with poor metabolic control and diabetes related complications even when the full diagnostic criteria of an eating disorder are not met. There is conflicting data in the literature regarding the prevalence of disordered eating behaviour in type 1 diabetes. The current study found that disordered eating behaviour is prevalent among 10% of the studied adolescents with type 1 diabetes. It was found to be more severe and frequent among those on basal-bolus insulin regimen than those on continuous subcutaneous insulin infusion. Moreover, it was correlated with depression, poor glycemic control, poor body image and long diabetes duration. Thus further studies are needed to verify the role of continuous glucose monitoring in the management of DEB among those with T1D.

DNMT3A and TET2; Potential Estimates of Generic DNA Methylation in Children and Adolescents with Obesity; Relation to Metabolic Dysregulation.

INTRODUCTION: The role of DNA methylation in metabolic dysregulation is emerging. However, the functional role of methylation in obesity and metabolic dysregulation is poorly understood. AIM: The aim of this study was to compare DNA methyltransferase-3A (DNMT3A) and ten-eleven translocase-2 (TET2) levels in children and adolescents with obesity to normal-weighed children and adolescents and to correlate them to various metabolic parameters. METHODS: Fifty children and adolescents with obesity were compared to 50 matched normal-weighed children and adolescents. Participants underwent assessment for anthropometric measurements, Tanner staging, acanthosis nigricans, and mean blood pressure percentile on three different occasions. TET2, DNMT3A, fasting lipids, and insulin were measured with calculation of the homeostatic model assessment insulin resistance (HOMA-IR). RESULTS: The median BMI SDS of the studied children and adolescents with obesity was 3.40, their mean TET2 was 178.40 ng/mL, and their mean DNMT3A was 2.18 ng/mL. TET2 is significantly lower (p = 0.009), while DNMT3A is significantly higher (p < 0.001) in children and adolescents with obesity than controls. Children and adolescents with obesity and insulin resistance have significantly lower TET2 (p = 0.012) and significantly higher DNMT3A (p = 0.013) than those without insulin resistance. Diastolic blood pressure percentile and HOMA-IR are positively correlated to DNMT3A (p < 0.001) and negatively correlated to TET-2 (p < 0.001). Multivariate logistic regression analysis revealed that TET2 and DNMT3A are independently associated with diastolic blood pressure percentile (p = 0.03 and p = 0.014, respectively) and HOMA-IR (p = 0.003 and p = 0.001, respectively). CONCLUSIONS: Children and adolescents with obesity have significantly higher DNMT3A and significantly lower TET2 than controls. This is more evident in those having insulin resistance than those without. DNMT3A and TET2 are independently associated with systemic hypertension and insulin resistance in children with obesity.

Circulating spexins in children with obesity: relation to cardiometabolic risk.

BACKGROUND/OBJECTIVES: The role of spexin (SPX) in energy metabolism, endocrinal homeostasis, and vasculopathy is emerging. However, scarce data are available about its role in childhood obesity and obesity-related vasculopathy. Hence, we aimed to assess the level of SPX in obese and normal-weight children, and to correlate it with aortic distensibility (AD) and aortic stiffness index (ASI). SUBJECTS/METHODS: Forty obese children were compared to 40 matched normal-weighed children. Weight, height, and body mass index (BMI) z score and mean blood pressure (Bl-Pr) percentile on three different occasions were obtained. SPX, fasting triglycerides, cholesterol, low-density (LDL), high-density lipoproteins (HDL), and insulin were measured with calculation of the homeostatic model assessment insulin resistance (HOMA-IR). Internal aortic diameter was measured with calculation of AD, strain (AS), and ASI. RESULTS: Children with obesity had significantly lower SPX (P = 0.004), HDL (P < 0.001), and AD (P < 0.001) and higher systolic Bl-Pr (P < 0.001), diastolic Bl-Pr (P < 0.001), LDL (P = 0.011), HOMA-IR (P < 0.001), and ASI (P < 0.001). Significant negative correlation was found between SPX and BMI z score (r = -0.646, P < 0.001), systolic Bl-Pr (r = -0.641, P < 0.001), diastolic Bl-Pr (r = -0.427, P < 0.001), HOMA-IR (r = -0.349, P = 0.028), and ASI (r = -0.389, P = 0.013), while significant positive correlation was found between SPX and AS (P < 0.001, r = 0.633) and AD (P < 0.001, r = 0.612). However, no significant correlation was found between SPX and age (r = -0.01, P = 0.953), TG (r = 0.048, P = 0.767), total cholesterol (r = -0.023, P = 0.887), LDL (r = -0.299, P = 0.061), and HDL (r = 0.193, P = 0.232). CONCLUSIONS: Children with obesity had significantly lower SPX than controls. SPX was correlated with BMI, Bl-Pr, HOMA-IR, and vasculopathy in children with obesity independent of their age and lipid profile. Further studies should explore the pathomechanism of SPX and its potential role in the management of obesity and obesity-related cardiometabolic risk.

Abdominal lymphadenopathy in children with Gaucher disease: Relation to disease severity and glucosylsphingosine.

Few case reports and series reported abdominal lymphadenopathy (ALN) in people with Gaucher disease (GD). However, it's prevalence among Gaucher population, clinical implications and potential biomarkers are unknown. Hence this study aims to assess the prevalence of ALN among children with GD & to correlate it to neutrophil-lymphocytic-ratio (NLR), platelet-lymphocytic-ratio (PLR) and glucosylsphingosine (Lyso-GL1). Fifty children with GD (14 type-1 and 36 type-3) on enzyme-replacement therapy (ERT) were compared to 50 matched healthy controls, focusing on history of pressure manifestations by ALN (diarrhea, constipation, abdominal pain, intestinal obstruction), and history of splenectomy, with calculation of severity scoring index (SSI). NLR, PLR and Lyso-GL1 were measured. Abdominal-ultrasound was done with assessment of liver and spleen volumes and ALN. CT-scan was done for those having significant lymphadenopathy. Twenty-six children with GD had ALN (52%). The most common presentations were abdominal-pain (22%) & constipation (18%), with intestinal-obstruction in 3 children (6%). Children with GD had significantly higher NLR (p < .001) and decreased PLR (p = .024) compared to controls. Interestingly, children with GD having ALN had significantly higher SSI (.012), Lyso-GL1 (p = .002) and NLR (p = .001) than those without ALN. Multivariate-logistic regression showed that ALN was independently related to Lyso-GL1 (p = .027), NLR (p = .023) and SSI (p = .032). Thus, ALN is a prevalent GD morbidity with wide clinical-spectrum ranging from asymptomatic cases to intestinal obstruction. ALN is related to SSI, NLR and Lyso-GL1 in children with GD.HighlightsChildren with GD had significantly higher NLR and lower PLR compared to controls.Children with GD having ALN had significantly higher SSI, Lyso-GL1 and NLR than those without ALN.ALN was independently related to Lyso-GL1, NLR and SSI in children with GD.

Disturbed sleep quality and architecture in adolescents with type 1 diabetes mellitus: Relation to glycemic control, vascular complications and insulin sensitivity.

BACKGROUND: Insufficient sleep duration and poor sleep quality have been linked to insulin resistance and impaired glucose metabolism. However, the relation between sleep disruption and type1 diabetes (T1D) hasn't been thoroughly explored. AIM: To study the association between sleep parameters and glycemic control, insulin resistance and micro-vascular complications among adolescent with T1D. METHODOLOGY: Sixty adolescents with T1D were compared to 60 matched controls. Diabetes-duration, insulin-therapy, fundus, Epworth Sleepiness Scale-Child Adolescent and the neuropathy disability score were assessed. Fasting lipids, fraction-C of glycosylated hemoglobin(HbA1c) and urinary albumin-excretion were measured with calculation of the insulin sensitivity score(ISS). Overnight polysomnography(PSG) was done. RESULTS: Adolescents with T1D had significantly lower sleep efficiency and rapid eye movement(REM) sleep than controls with significantly higher sleep onset latency, non-REM sleep and arousal index(P < 0.001). Although ISS was negatively correlated to total sleep time(P = 0.002); it was positively correlated to sleep efficiency(P < 0.001). HbA1C was negatively correlated to sleep efficiency(<0.001) and REM sleep(P = 0.003) and positively correlated to sleep onset latency(P = 0.005). T1D adolescents with micro-vascular complications had significantly lower sleep efficiency and REM sleep than those without micro-vascular complications. CONCLUSION: Poor sleep quality and architecture among adolescents with T1D are associated with impaired glycemic control, insulin resistance and micro-vascular complications.

Relationship of glycaemic derangement using continuous glucose monitoring system with sleep pattern among children with type 1 diabetes.

BACKGROUND: Glycaemic derangement has been linked to sleep disruption. However, the impact of glycaemic derangement on sleep pattern among children with type 1 diabetes (C-T1D) remains unraveled. AIM: To assess the effect of nocturnal hyperglycaemia and clinically significant (CS) hypoglycaemia on sleep pattern among C-T1D. METHODOLOGY: Thirty C-T1D were compared to 30 age and sex matched healthy siblings. Patients having other organ disease that might cause sleep disorders or on medications causing sleep disturbance were excluded. History included diabetes-duration, type and dose of insulin therapy, chronic diabetic-complications, and manifestations of sleep disorders. Epworth Sleepiness Scale-Child Adolescent was used. Continuous glucose monitoring system (CGMS) and overnight polysomnography were done and analysed. RESULTS: C-T1D had significantly lower sleep efficiency and significantly higher arousal index (AI), periodic limb movement index and apnoea-hypopnoea index compared to controls. Moreover, they had significantly longer sleep-onset latency, light sleep percentage, and shorter rapid eye movement percentage than controls. According to nocturnal CGMS readings, 15 C-T1D had nocturnal hyperglycaemia (50%), six experienced CS hypoglycaemia (20%), two had level-1 hypoglycaemia (6.7%), and seven were within the normoglycaemic range (23.3%). C-T1D experiencing nocturnal CS hypoglycaemia had significantly higher stage 3 sleep (P = 0.004) than controls. On the other hand, C- T1D experiencing nocturnal hyperglycaemia had significantly higher sleep onset latency (P = 0.013), light sleep percentage (P < 0.001), and AI (P < 0.001) than controls. Nocturnal CS hypoglycaemia was positively correlated to deep sleep duration, while hyperglycaemia was correlated to number of awakenings, sleep-onset latency, and light sleep duration. CONCLUSION: In children with T1D CS hypoglycaemia is associated with sleep deepening, while hyperglycaemia is associated with increased light sleep, sleep onset latency.

Ganglion Cell Complex Thinning in Young Gaucher Patients: Relation to Prodromal Parkinsonian Markers.

BACKGROUND: Patients with Gaucher disease (GD) have an increased risk for parkinsonism. Retinal thinning has been described in parkinsonism as an early nonmotor feature. Scarce reports have addressed retinal thickness changes in GD. OBJECTIVES: The objectives of this study were to compare ganglion cell complex (GCC) thickness in adolescents and young adults (AYAs) with GD with healthy control subjects, and to correlate it with the presence of parkinsonian features (PFs), clinical prodromal markers of parkinsonism, severity score index (SSI), and glucosylsphingosine (Lyso-GL-1). METHODS: This study included 48 AYAs with GD (11-29 years), 11 with manifest PFs (Group 1) and 37 with no PFs (Group 2), and 48 matched healthy control subjects (Group 3). Age of GD onset, disease duration, medication history, history of constipation, SSI, and hematological assessment were done. Neurocognitive evaluation included Parts I, II, and III of the Unified Parkinson's Disease Rating Scale (UPDRS), Wechsler Adult and Intelligence Scale and Wechsler Intelligence Scale for Children, Beck Depression Inventory (BDI), rapid eye movement sleep behavior disorder (RBD) scale, Munich Parasomnia Screening scale, and the olfactory dysfunction scale. Molecular analyses of the acid GBA gene and Lyso-GL-1 were done. Participants underwent full ophthalmological examination and optical coherence tomography with GCC thickness measurement. RESULTS: GCC was significantly thinner in Group 1 than in Groups 2 and 3 (P < 0.001), whereas no significant difference was found between Groups 2 and 3 (P = 0.977). In addition, a significant interocular GCC thickness difference was found among the studied AYAs with GD (P = 0.007). GCC correlated positively with total intelligence quotient (P < 0.001) and negatively with Lyso-GL-1 (P = 0.019), UPDRS (P = 0.004), and BDI (P = 0.029), but not with SSI (P = 0.874), GD type (P = 0.85), or genotype (P = 0.842). A significant negative relationship was found between GCC thickness and PFs (P = 0.001), parasomnia (P = 0.003), constipation (P = 0.031), RBD (P = 0.044), and hyposmia (P = 0.033). CONCLUSIONS: GCC thinning may be a promising biomarker for central nervous system neurodegeneration that has the potential to monitor early PFs among people with GD. © 2020 International Parkinson and Movement Disorder Society.